Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure

• Autor(a) principal: Arruda-Junior, Daniel F.
• Data de Publicação: 2016
• Outros Autores: Martins, Flavia L., Dariolli, Rafael, Jensen, Leonardo, Antonio, Ednei L. [UNIFESP], dos Santos, Leonardo, Tucci, Paulo J. F. [UNIFESP], Girardi, Adriana C. C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://repositorio.unifesp.br/handle/11600/57545; http://dx.doi.org/10.3389/fphys.2016.00293
• topic: vildagliptin; cardiorenal dysfunction; fluid retention; glucagon-like peptide-1; proteinuria; megalin

Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 +/- 5 vs. 45 +/- 3%, p < 0.05), and the isovolumic relaxation time decreased (33 +/- 2 vs. 27 +/- 1 ms